HLA-G genetic diversity and evolutive aspects in worldwide populations

• Autor(a) principal: Castelli, Erick C. [UNESP]
• Data de Publicação: 2021
• Outros Autores: de Almeida, Bibiana S., Muniz, Yara C. N., Silva, Nayane S. B. [UNESP], Passos, Marília R. S. [UNESP], Souza, Andreia S. [UNESP], Page, Abigail E., Dyble, Mark, Smith, Daniel, Aguileta, Gabriela, Bertranpetit, Jaume, Migliano, Andrea B., Duarte, Yeda A. O., Scliar, Marília O., Wang, Jaqueline, Passos-Bueno, Maria Rita, Naslavsky, Michel S., Zatz, Mayana, Mendes-Junior, Celso Teixeira, Donadi, Eduardo A.
• Tipo de documento: Artigo
• Idioma: eng
• Título da fonte: Repositório Institucional da UNESP
• Texto Completo: http://dx.doi.org/10.1038/s41598-021-02106-4; http://hdl.handle.net/11449/231561

HLA-G is a promiscuous immune checkpoint molecule. The HLA-G gene presents substantial nucleotide variability in its regulatory regions. However, it encodes a limited number of proteins compared to classical HLA class I genes. We characterized the HLA-G genetic variability in 4640 individuals from 88 different population samples across the globe by using a state-of-the-art method to characterize polymorphisms and haplotypes from high-coverage next-generation sequencing data. We also provide insights regarding the HLA-G genetic diversity and a resource for future studies evaluating HLA-G polymorphisms in different populations and association studies. Despite the great haplotype variability, we demonstrated that: (1) most of the HLA-G polymorphisms are in introns and regulatory sequences, and these are the sites with evidence of balancing selection, (2) linkage disequilibrium is high throughout the gene, extending up to HLA-A, (3) there are few proteins frequently observed in worldwide populations, with lack of variation in residues associated with major HLA-G biological properties (dimer formation, interaction with leukocyte receptors). These observations corroborate the role of HLA-G as an immune checkpoint molecule rather than as an antigen-presenting molecule. Understanding HLA-G variability across populations is relevant for disease association and functional studies.